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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Identification of candidate metabolite biomarkers for metabolic syndrome and its five components in population-based human cohorts.
Cardiovasc. Diabetol. 22:141 (2023)
Background: Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its associated risk factors to better understand the complex interplay of underlying signaling pathways. Methods: We quantified serum samples of the KORA F4 study participants (N = 2815) and analyzed 121 metabolites. Multiple regression models adjusted for clinical and lifestyle covariates were used to identify metabolites that were Bonferroni significantly associated with MetS. These findings were replicated in the SHIP-TREND-0 study (N = 988) and further analyzed for the association of replicated metabolites with the five components of MetS. Database-driven networks of the identified metabolites and their interacting enzymes were also constructed. Results: We identified and replicated 56 MetS-specific metabolites: 13 were positively associated (e.g., Val, Leu/Ile, Phe, and Tyr), and 43 were negatively associated (e.g., Gly, Ser, and 40 lipids). Moreover, the majority (89%) and minority (23%) of MetS-specific metabolites were associated with low HDL-C and hypertension, respectively. One lipid, lysoPC a C18:2, was negatively associated with MetS and all of its five components, indicating that individuals with MetS and each of the risk factors had lower concentrations of lysoPC a C18:2 compared to corresponding controls. Our metabolic networks elucidated these observations by revealing impaired catabolism of branched-chain and aromatic amino acids, as well as accelerated Gly catabolism. Conclusion: Our identified candidate metabolite biomarkers are associated with the pathophysiology of MetS and its risk factors. They could facilitate the development of therapeutic strategies to prevent type 2 diabetes and cardiovascular disease. For instance, elevated levels of lysoPC a C18:2 may protect MetS and its five risk components. More in-depth studies are necessary to determine the mechanism of key metabolites in the MetS pathophysiology.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Amino Acids ; Bcaas ; Cardiovascular Disease ; Hyperglycemia ; Hypertension ; Lysophosphatidylcholines ; Metabolic Syndrome ; Metabolomics ; Obesity ; Phosphatidylcholines; Insulin-resistance; Oxidative Stress; Obesity; Individuals; Glutathione; Disease; Profile; Health; Serine; Acids
ISSN (print) / ISBN
1475-2840
e-ISSN
1475-2840
Zeitschrift
Cardiovascular Diabetology
Quellenangaben
Band: 22,
Heft: 1,
Artikelnummer: 141
Verlag
BioMed Central
Verlagsort
Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Translational Genomics (ITG)
Institute of Epidemiology II (EPI2)
Institute of Experimental Genetics (IEG)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Epidemiology II (EPI2)
Institute of Experimental Genetics (IEG)
CF Metabolomics & Proteomics (CF-MPC)